"Adaptive" behavior of ligand-gated ion channels: constraints by thermodynamics

Biophysical Journal
M D Stern

Abstract

The calcium-induced calcium release channel of the cardiac sarcoplasmic reticulum has been reported to inactivate in a novel manner (termed "adaptation"), which permits reactivation by exposure to successively higher concentrations of calcium. I examined the limitations placed by thermodynamics on the possible kinetic mechanisms for such behavior. The mechanism suggested by Gyorke and Fill, in which the affinity of a calcium-binding site decreases during adaptation, is not thermodynamically feasible for a passive system, but requires an external input of free energy. Possible sources of such energy are 1) metabolic energy, which is excluded by the fact that adaptation was observed in isolated channels in the absence of ATP, or 2) coupling of ion permeation to gating, for which there is currently no evidence. I derived a general limit on the thermodynamic feasibility of a sequence of channel activations and adaptations, irrespective of channel kinetics, from the requirement that the free energy must decrease during the spontaneous evolution of the system from the state existing immediately after a step increase in [Ca2+] to the state of maximum open probability that follows. The opening of the channel must involve an increase in...Continue Reading

Citations

Apr 15, 2009·Developmental Psychobiology·Mariana SchroederAron Weller
Dec 16, 1997·Molecular Pharmacology·C Dettbarn, P Palade
Sep 25, 2002·Physiological Reviews·Michael Fill, Julio A Copello

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